C-Myc



Overview
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The c-Myc oncogene encodes a transcription factor, c-Myc protein, which is involved in the regulation of the cell cycle. C-Myc belongs to the Myc family of proteins including B-Myc, L-Myc, N-Myc, and s-Myc. c-Myc is a b-HLH-LZ (basic helix-loop-helix-leucine zipper) protein that must form a heterodimer with another b-HLH-LZ protein, Max, in order to bind DNA and activate transcription. Mutations in myc proteins or overexpression of their encoding genes have been linked to several forms of cancer, among these are lymphoma, myeloma, liver, lung, and breast cancer.

Origins of C-myc
In 1911 a virologist named Peyton Rous saw that sarcoma in chickens could be transmitted through cell free extracts from the sarcoma tumors. This suggested that a virus was possibly the etiologic agent of the sarcoma. To see if it was true scientists studied an avian retrovirus which was found to induce myeloid leukemia, sarcomas, liver, kidney, and other tumors. They also found a gene in the body named V-myc. V-myc (myelocytomatosis viral oncogene homolog 1) is the gene in the body that aided the virus in causing cancer in the chickens. Soon after they found genes in humans with Burkitt's Lyphoma that had a similar makeup to the V-myc gene. Later they found that C-myc like V-myc causes cancer when the gene is changed or affected by something else.

C-myc Bonding
The c-myc protein cannot homodimerize without the protein Max. Max can sometimes heterodimerize with Mad family proteins. The Mad-Max, Mad3-Max, Mad4-Max, and Mnt-Max heterodimers are antagonist of c-myc. The myc-max connection is unstable which allows for high populations of dissociated monomers and it impedes reassortment dictated by the level of expression of c-myc, mad, and mxi1 genes and transduction of cell growth and differentiation signals. For oncogenic activity to occur c-myc must bind with the Max protein. All max proteins will bind to the same DNA sequence.

General Functions of C-myc
C-myc is used in cell cycle entry, proliferation, and differentiation. C-myc also helps to bind DNA which activates transcription. The c-myc lives a very short life. It is controlled by the level and temporal pattern of expression of their corresponding gene. Without C-myc an organism is unable to survive since there is nothing allowing cells to differentiate or proliferate. The organisms cannot survive after the pre-T-cell receptor proliferation is unable to be completed.

C-myc is also involved in the body's system of remembering past diseases. T-cells help the body to remember diseases it has previously had. C-myc controls the regulation of T-cells. Without C-myc the T-cells would not be triggered to multiply when a disease that the body has seen before infiltrates the body again.

C-myc's Role in Cancer
C-myc's proliferation is induced by enhancers that help to increase immunoglobin genes functions. It has been seen that the greater amount of C-myc present the higher the chances that cancer is also present. Cancer is often able to grow best in people with weakened immune systems. Since the immune system is weak the T-cells pass over the cancer without noticing that anything is wrong. This combined with the fact that these enhancers cause C-myc to rapidly produce cells is causing cancer in a body that cannot fight it off. The newly formed cells continue to grow on each other. This causes a tumor that is cancerous that is unnoticed. The most common form of cancer that c-myc plays a role in is Burkitt's Lymphoma.

C-myc can not be induced by enhancers unless it has translocated from its normal spot on chromosome 8 to another chromosome. When C-myc is translocated to a spot next to a gene that is an immunoglobin enhancer gene it can eventually become a tumor. The reason for this is that when these genes code for the body to make more B-cells, they inadvertantly turn on the gene adjacent to them as well. Since C-myc is now the new gene next to the enhancer gene it starts to create a lot of C-myc RNA and it then becomes C-myc transcription factor. The factor then induces cells to divide very rapidly. The cells then keep dividing until they have formed a cancerous tumor. This process shows that one cell is all that is needed to create a tumor. It has been estimated that 100,000 of the cancer related deaths per year in the United Sates are associated with changes in the C-myc gene or its expression.

Experiments with C-myc
An experiment was done to see if mice could survive embryonic development without the C-myc gene. This was done by using a mutation to make the C-myc allele null at the protein level. They gave some of the embryos one correct copy of the allele and others no correct copy. The homozygous mice (two null C-myc alleles), died between 9.5 and 10.5 days of gestation. The mice also were smaller and had many health problems. This showed that C-myc is vital to the development of embryos of organisms.

Additional Resources
For additional information, see: Cancer

For additional information, see: Oncogenes

For additional information, see: Transcription and RNA Processing